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Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.
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This paper reviewed three aspects of risk factors of catheter-related thrombosis in critically ill children with central venous access devices, including the child's own factors, catheter-related factors and external factors. It summarized the main research advances of preventive measures such as the strengthen assessment of pre-catheterization, drug and mechanical prevention of thrombosis, control of catheter-related other complications, thrombus screening routinely, risk assessment model is used. It is to provide experience for early clinical identification and formulation of preventive measures, so as to reduce the occurrence of catheter-related thrombosis in critically ill children and promote the central venous access device used safely in PICU.
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Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Subject(s)
Animals , Male , Apoptosis , Astrocytes , Metabolism , Benzyl Alcohols , Blood-Brain Barrier , Metabolism , Brain , Metabolism , Brain Edema , Calcium , Metabolism , Glucosides , Glutamic Acid , Metabolism , Microglia , Metabolism , Neurons , Neuroprotective Agents , Oxidative Stress , Rats, Sprague-Dawley , Subarachnoid Hemorrhage , MetabolismABSTRACT
Objective To evaluate the therapeutic efficacy and safety of micro-invasive craniopuncture scavenging technique (MPST) for treatment of intracranial hematoma in patients with hypertensive cerebral hemorrhage (HICH).Methods All the clinical randomized controlled trial (RCT) studies published on MPST and internal medicine conservative treatment of HICH were searched via computer screening of databases including Cochrane clinical trials database, the Chinese biomedical literature database (CBM), Chinese periodical network full-text special topic database, Chinese science and technology periodical database and electronic periodicals database of Wanfang from January 2006 to January 2017. The study group was given the MPST plus basic treatment, and the control group was given conservative treatment. The studies collected meeting the eligible criteria were sorted and analyzed by the software RevMan 5.0, the differences in therapeutic effect and mortality were compared between the two groups, and a funnel chart was plotted to analyze the potential publication bias.Results A total of 13 RCTs published studies consistent with the eligible criteria were found, including1556 patients. The Meta-analysis showed that the effective rate in the study group was significantly higher than that in the control group [odds ratio (OR) = 4.29, 95% confidence interval (95%CI) 3.33 - 5.53,P < 0.01]; the fatality rate was markedly lower than that of the control group (OR = 0.25, 95%CI 0.19 - 0.35,P < 0.01). The funnel graph showed that each study had asymmetrical scatter plot of the variable quantity of research results, indicating a publication bias being present, which might be related to the subjectivity of the researchers in publishing their results.Conclusions Using MPST to treat HICH can significantly improve the therapeutic efficiency and reduce deterioration rate. However, due to the low quality of clinical research, it is necessary to carry out rigorous andmulti-center randomized controlled studies to further confirm the results.
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Objective To observe the clinical efficacy of needling a group of acupoints for choke plus rehabilitation training in treating post-stroke deglutition disorder.Method Ninety patients with post-stroke deglutition disorder were randomized into a treatment group and a control group, 45 cases in each group. In addition to the conventional treatment, the control group also received swallowing rehabilitation training, and the treatment group received acupuncture ata group of acupoints for chokeas the major intervention(Aqiang point, Zhiqiang point, Tunyan point, Tiyan point and Fayin point, all extra) besides the intervention given to the control group, both for 3 successive treatment courses. Before and after theintervention, the National Institute of Health Stroke Scale (NIHSS), Videofluoroscopic Study (VFSS), post-stroke swallowing scale of traditional Chinese medicine (TCM) (TCM scale for short), and the occurrence rate of relevant complications were comparedbetween the two groups.Result The total effective rate was 97.8% in the treatment group, significantly higher than 84.4% in the control group (P<0.05); the scores of NIHSS, VFSS and TCM scale in the treatment group were superior to those in the control group (P<0.05);the NIHSS, VFSS and TCM scale scores in the treatment group were superior to those in the control group after the intervention (P<0.05);24 cases in the control group presented complications versus 8 cases in the treatment group (P<0.05).Conclusion Acupuncture at the points group for chokepredominantlyplus rehabilitation training can effectively improve post-stroke deglutition disorder and reduce the occurrence of complications, with satisfactory safety and consistency.
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Objective: To investigate HDAC5 expression in gastric cancer cell lines and its effects on the proliferation and apoptosis of the gastric cancer line SGC-7901. Methods: The expression patterns of HDAC5 and Twist1 in gastric cancer cell lines and normal gastric mucosal cells were detected by Western blot. The effects of HDAC5 and Twist1 on the proliferation and apoptosis of SGC-7901 cells were analyzed by MTT and flow cytometry, respectively. Results: The expression of HDAC5 and Twist1 in gastric cancer cell lines were significantly higher than that in normal gastric mucosal cells (P<0.05). HDAC5 knockdown significantly down-regulated Twist1 expression,inhibited cell proliferation, and induced apoptosis in SGC-7901 cells, whereas HDAC5 overexpression exhibited an opposite effect (P<0.05). Moreover, Twist1 knockdown significantly inhibited cell proliferation and induced apoptosis in SGC-7901 cells (P<0.05). Conclusion:HDAC5 may promote cell proliferation and inhibit apoptosis in gastric cancer cells by upregulating Twist1 expression, thus promoting the initiation and development of gastric cancer.
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Objective:To evaluate the micro-push-out bond strengths of prefabricated glass fiber posts with poly-dopamine functionalized to root dentin using resin cements, contrasted with silane treatment. Methods:In the study, 30 glass fiber posts were randomly divided into 3 groups ( 10 posts in each group) for different surface treatments. Group 1, treated with poly-dopa; Group 2, treated with silane coupling agent for 60s;Group 3, no surface treatment (Control group). The 30 extracted human, single-rooted teeth were endodontically treated and a 9 mm post space was prepared in each tooth with post drills provided by the manufacturer. Following post cementation, the specimens were stored in distilled water at 37 ℃ for 7 days. The micro-push-out bond strengths were tested using a universal testing machine (0. 5 mm/min), and the failure modes were examined with a stereomicroscope. The data of the three groups were statistically analyzed using the one-way ANOVA test(α= 0. 05). Results:The bond strengths were (7. 909 ± 1. 987) MPa for Group 1, (5. 906 ± 0. 620) MPa for Group 2, and 4. 678 ± 0. 910 MPa for Group 3 . The bond strength of poly-dopamine group was significantly higher than that of the silane group (P<0. 05). Conclusion: Contrasted with silane treatment, surface poly-dopamine functionaliza-tion was confirmed to be a more reliable method for improving the bond strength of resin luting agents to fiber posts.
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Objective:To analyze the biomechanics trait of one-piece computer aided design and com-puter aided manufacture ( CAD/CAM ) zirconia post and core by the three-dimensional finite element . Methods:The three-dimensional finite element models of three upper central incisors restored with one -piece CAD/CAM zirconia post and core ( group 1 ) , refabricated zirconia post and hot-pressed porcelain core ( group 2 ) , and cast gold alloy post and core ( group 3 ) were built by geometry method respectively . 100 N vertical loading through the central incisor models long axis and 100 N loading along directing at an angle of 45°with the models long axis were used to imitate the central incisor stress state in biting and mandible physiological protraction movement .Results:Under vertical loading , the restored teeth without dentin ferrule, the maximum Von-Mises stress value of the tooth root in group 1 was the least(11.02 N), which was the largest (13.17 N)in group 2.The stress became weaker from the upper to the lower of the tooth root.The maximum Von-Mises stress value of the tooth root , post and core became smaller while the restored teeth with the 2.0 mm high dentin ferrule.Under directing at an angle of 45°loading, without the design of dentin ferrule in the restored teeth , the maximum Von-Mises stress value of the post and core in group 1 was the greatest(20.45 N), while that stress of post and core in group 3 was the smallest (13.61 N).With 2.0 mm high dentin ferrule design in the restored teeth , the tooth root stress became weaker.The maximum Von-Mises stress value of the tooth root was the greatest (14.10 N) in group 3, but which was the lowest (13.38 N) in group 1.Conclusion:The results of the three-dimensional finite element analysis infers that one-piece zirconia post and core restoration is more beneficial to disperse the bite force than the prefabricated zirconia post and the cast gold alloy post and core .The one-piece of zirconia post and core is good to protect the teeth and keep the restoration intact .
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<p><b>OBJECTIVE</b>To verify the efficacy and safety of post-marketed fleabane injection combined with Dengzhan Shengmai capsules in the treatment of ischemic stroke (IS).</p><p><b>METHOD</b>A multicentre, prospective, practical, randomized controlled study was carried out to compare the efficacy and safety of Dengzhan group (n = 343) and western medicine group (n = 335), appling "clinical study central stochastic system". The treatment of Dengzhan group is using fleabane injection in acute stage and Dengzhan Shengmai capsules in convalescence. The primary indexes of effect evaluation are the important outcome events in 360 days' follow-up, including mortality, recurrence, disability and quality of life to reflect the effect of clinical study. The indexes of safety evaluation involve laboratory examination results and incidence of adverse events.</p><p><b>RESULT</b>After 360 days' follow-up, 4 people died of IS in Dengzhan group, and the mortality rate of which is 1.17%, while 16 died in Western medicine group (WM group), and the mortality rate is 4.78%, suggesting that the mortality rate of Dengzhan group is significantly lower than WM group (P<0.05). Eleven cases recurred in Dengzhan group, and the recurrence rate of which is 3.21%, while 12 recurred in WM group, and the recurrence rate is 3.59%, indicating that the recurrence rate of Dengzhan group is slightly lower than WM group. The disability rate of Dengzhan group is 39.53%, among which the rate of severely disabled cases are 1.49%, while the disability rate of WM group is 40.13%, among which the rate of severely disabled cases are 3.13%, suggesting that the disability rate of Dengzhan group is lower and the severity of disability is also lighter than WM group. In the field of quality of life, the activity ability and the upper limb function store of stroke patients in Dengzhan group improved far much better than WM group (P<0.05). Analysis of safety suggested that, adverse events occurred in 11 cases in Dengzhan group, among which 4 cases is related with the drug treatment, the incidence of adverse events of which is 1.17%, and the main manifestations involve fever and chilling, rash, nausea, dizziness, palpitation, etc. which were all appeared after the treatment of fleabane injection, and disappeared 1 to 2 days after drug withdrawal. 13 cases occurred abnormal liver function and 2 cases abnormal kidney function in Dengzhan group. According to the judgment of clinical physicians, 3 case of ALT abnormality is possibly related to the treatment, the others are all unrelated with the treatment.</p><p><b>CONCLUSION</b>Fleabane injection and Dengzhan Shengmai capsules are all safe and effective TCM in the treatment of ischemic stroke.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Brain Ischemia , Drug Therapy , Capsules , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal , Therapeutic Uses , Erigeron , Injections , Product Surveillance, Postmarketing , Prospective Studies , Stroke , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke.</p><p><b>METHOD</b>Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time.</p><p><b>RESULT</b>Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed.</p><p><b>CONCLUSION</b>Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Brain Ischemia , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal , Therapeutic Uses , Injections , Medicine, Chinese Traditional , Product Surveillance, Postmarketing , Stroke , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of panaxynol (PAN) on delayed type hypersensitivity and possible mechanism.</p><p><b>METHOD</b>Allergic contact dermatitis (ACD) was induced by DNCB as a delayed type hypersensitivity (DTH) model to observe effect of PAN on auricle inflammation including pathological injury. Proliferation of T lymphocytes was induced by ConA and measured by MTf method. IFN-gamma secretion of splenocyte induced by ConA was detected by ELISA.</p><p><b>RESULT</b>The swelling degree of auricle and pathological injury in ACD mice was reduced significantly by treated with PAN in induction phase. Proliferation of T lymphocytes induced by ConA in vitro was inhibited significantly by PAN, By contrast, no detectable effect was observed in resting splenocyte. IFN-y induced by ConA in splenocytes was inhibited markedly by PAN from 10 micromol x L(-1) and from 6 h.</p><p><b>CONCLUSION</b>The results showed that DTH was inhibited by PAN mainly in induction phase and this effect may be related with the inhibition on T lymphocytes proliferation and secretion of IFN-gamma.</p>
Subject(s)
Animals , Female , Male , Mice , Cell Proliferation , Concanavalin A , Metabolism , Dermatitis, Allergic Contact , Drug Therapy , Allergy and Immunology , Metabolism , Diynes , Pharmacology , Therapeutic Uses , Fatty Alcohols , Pharmacology , Therapeutic Uses , Interferon-gamma , Bodily Secretions , Mice, Inbred ICR , Spleen , Pathology , Bodily Secretions , T-Lymphocytes , PathologyABSTRACT
Phosphoglycerate mutase (PGAM) is a key enzyme in glycolytic pathways. With PCR technique based on an EST identified in our lab, a novel gene named SjPGAM (GenBank Accession No. EU374631) was cloned. Sequence analysis revealed that the ORF of SjPGAM gene contained 753 nucleotides, encoding 250 amino acids, and the molecular weight was about 28.26 kD. Real-time PCR analysis showed that the mRNA level of SjPGAM was much higher in the 14 days and 19 days schistosomula than other stages, suggesting that the gene was a schistosomula stage differential expression gene. The SjPGAM cDNA fragment was subcloned into an expression vector pET-28a (+) and transformed into Escherichia coli BL21 cells. In the presence of IPTG, the 31 kD fusion protein was expressed in included bodies. Western blotting revealed that the fusion protein could be recognized by the rabbit serum anti-Schistosoma japonicum adult worm antigen preparation. The study provides important basis for investigating the mechanism of the PGAM in the glycolytic pathways of Schistosoma japonnicum.
Subject(s)
Animals , Male , Rabbits , Cloning, Molecular , Escherichia coli , Genetics , Metabolism , Phosphoglycerate Mutase , Genetics , Allergy and Immunology , RNA, Messenger , Genetics , Metabolism , Recombinant Proteins , Genetics , Metabolism , Schistosoma japonicum , Genetics , Schistosomiasis japonica , Allergy and Immunology , ParasitologyABSTRACT
Objective: To measure the fracture strength of the posterior galvano-ceramic bridges made by Ni-Cr pontic fired bonding galvano caps with highly temperature-resistant adhesive and to provide re-ference data for clinical application. Methods: A standard low dental cast was achieved with 46 missing. Five posterior galvano-ceramic bridges made by Ni-Cr pontic fired bonding galvano caps, with abutments being 47 and 45 . The low dental cast was fixed on the panel of the universal testing machine, vertical load given on the central of the pontic as the velocity of 2 mm/min. Results: The fracture strength of the posterior galvano-ceramic bridges made by Ni-Cr pontic fired bonding galvano caps was (877.00?126.53) N, the fracture strength of the metal frame was (1 448.94?51.02) N. Conclusion: Posterior galvano-ceramic bridges made by Ni-Cr pontic fired bonding galvano caps could endure the normal human occlusal force.
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Objective To research the influences of gambogic acid on rats'cytochrome P450 isoforms by using the Cocktail probe drugs. Methods Rats were randomly divided into several groups. One group of rats received gambogic acid solution containing 0.5 %CMC-Na (2 mg?mL-1,once per day) orally for six days. At the same time,the rats in the other group received 0.5 %CMC-Na solution serving as blank control group. Blood samples were collect at different time point,and the plasma concentration of cocktail probe drugs was determined by HPLC. Results There was insignificant difference of caffeine and dapsone metabolism between the gambogic acid group and the blank group,but the chlorzoxazone was eliminated faster in the gambogic acid group,and the half life of chlozoxazone was shorter. Conclusion Gambogic acid has no significant influence on the cytochrome P450 isoforms of CYP1A2 and CYP3A4,but has an induction on the CYP2E1.